Diabetes | Biosplice

Overview of Diabetes

Diabetes is a chronic metabolic disorder characterized by elevated blood sugar levels due to the body’s inability to produce or effectively utilize insulin. The two primary types of diabetes are Type 1 diabetes (T1D), an autoimmune condition that destroys insulin-producing beta cells in the pancreas, and Type 2 diabetes (T2D), which involves insulin resistance and subsequent beta-cell dysfunction. Both types can lead to significant health complications if not properly managed¹.

Currently available therapies for diabetes include lifestyle modifications, hypoglycemic agents (such as sulfonylureas, meglitinides, and SGLT2 inhibitors), incretin-based therapies (GLP-1 agonists and DPP-4 inhibitors), insulin sensitizers (thiazolidinediones), and insulin therapies. While these treatments can help manage blood glucose levels, they do not address the underlying issue of beta-cell loss². Consequently, there is a critical need for therapies that can regenerate and restore beta-cell function.

References

American Diabetes Association Professional Practice Committee. (2024). Diagnosis and classification of diabetes: Standards of care in diabetes—2024. Diabetes Care, 47(Supplement_1), S20–S42. https://doi.org/10.2337/dc24-S002
American Diabetes Association Professional Practice Committee. (2024). Pharmacologic approaches to glycemic treatment: Standards of care in diabetes—2024. Diabetes Care, 47(Supplement_1), S158–S178. https://doi.org/10.2337/dc24-S009

Preclinical

Mechanism of Action Therapeutic Potential

Mechanism of Action

DYRK1A (Dual-specificity tyrosine-phosphorylation-regulated kinase 1A) is a protein kinase involved in various cellular processes, including cell proliferation and differentiation. Recent research has identified DYRK1A as a promising target for diabetes treatment due to its role in regulating beta-cell proliferation (Vetere, Choudhary, Burns, & Wagner, 2014). Inhibiting DYRK1A has been shown to induce the proliferation of pancreatic beta cells, which are crucial for insulin production. This discovery paves the way for regenerative therapies aimed at restoring beta-cell mass and function in diabetic patients.

Therapeutic Potential

The therapeutic potential of DYRK1A inhibitors in diabetes management is substantial. By potentially increasing the mass of insulin-producing beta cells, these inhibitors could help restore normal insulin production and improve blood glucose control in diabetic patients. Biosplice Therapeutics has developed some of the most selective and potent DYRK1A inhibitors currently available (Mittapalli et al, 2024). Current research focuses on optimizing these inhibitors in preparation for IND-enabling studies.

Studies indicate that combining DYRK1A inhibitors with other therapeutic agents, such as GLP-1 receptor agonists can synergistically enhance beta-cell proliferation and function (Ackeifi et al, 2020). This combination therapy approach holds promise for developing more effective and selective diabetes treatments.

Diabetes affects over 500 million people worldwide (International Diabetes Federation, 2023), representing a significant global health burden. The potential market for effective diabetes therapies is vast, as current treatments often fail to address the root cause of the disease. The development of DYRK1A inhibitors could revolutionize diabetes management by offering a regenerative approach, potentially benefiting millions of patients.

Publications

Ultra-selective DYRK1A/B Inhibitors Mediated β-Cell Proliferation In Vitro and In Vivo

American Diabetes Association Scientific Sessions | June 21 - 24, 2024